Lecithin:cholesterol acyltransferase(CLCAT) deficiency is characterized by cloudy cornea, anemia, and renal disease. Fish eye disease(FED) is characterized by partial LCAT deficiency with similar features except for the absence of renal disease. Despite low levels of HDL most pts do not develop CAD. The objective of this study was to determine the mechanism of increased CAD in FED pts by analysis of the kinetics of apoA-I, apoA-II, and LDL. Autologous 125I-LDL and nl 131I-LDL was injected in 2 FED pts with CAD and 1 FED pt without CAD. The fractional catabolic rate (FCR) of the autologous and nl LDL were similar. However, both FED with CAD(0.28d-1)and FED without CAD(0.27d-1) had delayed catabolism of LDL compared to nls(0.40d-1) or pts with CLCAT deficiency without CAD(0.70d-1). ApoB was increased in FED with CAD vs without CAD (147 vs 79mg/dl). The production rate of FED pts with CAD was increased over FED without(18.5 vs 9.4mg/kg.d). 125I-apoA-I and 131I-apoA-II was injected into the same FED pts. ApoA-I and apoA-II were decreased in both groups (27 and 4mg/dl). The FCR of apoA-I in both groups were similar (0.74d-1) but this was very rapid compared to nls (1.54d-1). ApoA-II catabolism was more rapid in FED without CAD compared to FED with CAD (0.94 vs 0.66d-1) but both were faster than nls (1.64d-1). The slower apoA-II rate was due to a shift of apoA-II to larger remnant particles postprandially by centrifugation and FPLC. In summary: 1)The decreased HDL in FED is due to increased catabolism of apoA-I and apoA-II. 2)FED with CAD had increased apoB and LDL when compared to FED without CAD. 3)The increased LDL in FED with CAD is due to both increased LDL synthesis and delayed catabolism. 4)Increased LDL and decreased HDL characterize the FED pt with CAD.